Sterols are cyclic hydrocarbon molecules that help regulate the fluidity of cellular membranes. Sterols are essential components in all eukaryotic cells, and inhibitors that completely block sterol synthesis will block cell division and generally lead to cell death. In humans the predominant membrane sterol is cholesterol, which serves its structural role in membranes, and also serves as the precursor to hormones, bile salts, and modified membrane components. In fungi, the predominant sterol is often ergosterol, which follows the same biosynthetic pathway as cholesterol but contains an additional methyl group and altered double-bond placements. In plants there are multiple sterols working in different combinations, with stigmosterol and sitosterol as the most common components. The plant sterols tend to have 29 carbons, versus the 28 carbons of ergosterol, and the 27 carbons of cholesterol, but all are synthesized from the common precursors squalene and lanosterol.
The biosynthetic pathway leading to the final sterol products is long and complicated, requiring significant amounts of cellular energy to drive the multiple NADH (and/or NADPH) driven reduction steps. One enzyme in this pathway, sterol delta-14 reductase has been extensively studied in fungi because of its involvement in ergosterol synthesis (Lai et al. (1994) Gene 140: 4149; Parks et al. (1995) Lipids 30: 227–230). Mutants in sterol delta-14 reductase accumulate the aberrant sterol ignosterol, and can be supplemented with nutrients and growth conditions to survive (Palermo et al. (1997) Curr Genet 32: 93–99; Crowley et al. (1996) J Bacteriol 178: 2991–2993). The gene encoding this enzyme has been cloned and studied as a target for fungicidal agents (Marcireau et al. (1992) Curr Genet 22: 267–272; Barrett-Bee and Dixon (1995) Acta Biochim Pol 42: 465–479).
Prior to the instant invention, no plant sterol delta-14 reductase genes have been isolated. Availability of such plant genes will enable one to alter sterol production and/or composition in plants, to identify compounds that may be used as novel herbicides and fungicides, and to identify mutants of these genes that are resistant to these herbicides that will enable the production of herbicide-resistant crops.